Un nuevo objetivo terapéutico en la lucha contra la trombosis: Glicoproteína VI

Un nuevo objetivo terapéutico en la lucha contra la trombosis: Glicoproteína VI

El ISAR PLASTER, estudio en fase 2, evaluó el Revacept, una proteína monoclonal que inhibe la GPVI en pacientes con angioplastia coronaria programada. La agregación plaquetaria es un factor clave del proceso de trombosis que ocurre en el contexto del accidente de placa u oclusión de un stent coronario. La plaqueta sufre dos procesos consecutivos

El ISAR PLASTER, estudio en fase 2, evaluó el Revacept, una proteína monoclonal que inhibe la GPVI en pacientes con angioplastia coronaria programada.


La agregación plaquetaria es un factor clave del proceso de trombosis que ocurre en el contexto del accidente de placa u oclusión de un stent coronario. La plaqueta sufre dos procesos consecutivos para colaborar en la formación del trombo: el primero, que se denomina activación plaquetaria, lleva a la expresión de los receptores que permiten la unión de una plaqueta con otra, y el segundo, llamado agregación plaquetaria que consiste finalmente en dicha unión.

La inhibición de este proceso tiene impacto en la reducción de eventos clínicos que sufren los pacientes. Hasta el día de hoy, esta inhibición se ha logrado con fármacos que actúan directamente sobre distintos objetivos plaquetarios: 1) producción de tromboxano, con la aspirina, 2)  receptores de ADP (P2Y12) con clopidogrel, ticagrelor, prasugrel o cangrelor 3) receptores de fibrinógeno (IIbIIIa) con tirofibán, eptifibitide y abxicimab 4) receptor de trombina (PAR-1) con Vorapaxar. Todos estos mecanismos tienen en común bloquear la agregación plaquetaria de forma continua, y de esta manera afectar la hemostasia sistémica, traduciendo esto último en un mayor riesgo de sangrado.

El propósito de lograr inhibir el proceso de agregación plaquetaria potentemente sin aumentar el riesgo hemorrágico ha llevado a la búsqueda de otros objetivos terapéuticos. Si pudiéramos actuar sobre los activadores de las plaquetas y no sobre ellas, hipotéticamente no afectaríamos la hemostasia general.

Uno de los principales factores que llevan a la activación plaquetaria es el colágeno. Las fibras de colágeno representan el componente con mayor poder protrombótico de las placas ateroscleróticas, y al ser expuestas por la erosión o rotura de la capa protectora, se unen al receptor plaquetario denominado glicoproteína VI (GPVI) favoreciendo la activación plaquetaria. Este fenómeno impresiona ser central en los procesos de infarto de miocardio y accidente cerebrovascular, pero menos relevante en la hemostasia fisiológica.

En los últimos años se ha puesto énfasis en el desarrollo de moléculas que actúen sobre este “target” terapéutico, aspirando a que sólo se afecte la agregación plaquetaria a nivel del sitio de rotura de la placa, y de esta manera se reducirían los eventos hemorrágicos asociados. Revacept es una proteína monoclonal que inhibe la GPVI y se administra por vía endovenosa. ACT017 es un anticuerpo monoclonal contra la GPVI. En el estudio ISAR PLASTER, recientemente publicado en JAMA, 334 pacientes sometidos en forma programada a una angioplastia coronaria fueron tratados con revacept 80 mg, revacept 160 mg o placebo añadido al tratamiento médico basado en aspirina y clopidogrel. El estudio tuvo como punto final la reducción de la mortalidad o los infartos periprocedimientos, sin encontrar diferencias en ellos. El punto final de seguridad de sangrados BARC 2 o más no se modificó entre los grupos. El estudio fue un fase 2 y pese a no alcanzar un “pretencioso” punto final primario, demostró la seguridad de la droga al no aumentar los eventos hemorrágicos significativos. El próximo paso es el inicio de estudios en pacientes con síndromes coronarios agudos o con alto riesgo de sufrirlos para poner a prueba la hipótesis de protección de eventos.

En conclusión, el receptor glicoproteíco VI luce como un interesante objetivo terapéutico, atractivo por la posibilidad de inhibir la agregación en lugares específicamente necesarios sin afectar la hemostasia general del paciente. Los próximos años serán claves para evaluar si el revacept u otro medicamento de la familia aportan utilidad en la práctica clínica.

 Ver link AQUI

Lecturas recomendadas

1-Mayer K, Hein-Rothweiler R, Schüpke S et al. Efficacy and Safety of Revacept, a Novel Lesion-Directed Competitive Antagonist to Platelet Glycoprotein VI, in Patients Undergoing Elective Percutaneous Coronary Intervention for Stable Ischemic Heart Disease: The Randomized, Double-blind, Placebo-Controlled ISAR-PLASTER Phase 2 Trial. JAMA Cardiol. 2021 Mar 31:e210475.

2-Beziere N, Fuchs K, Maurer A et al. Imaging fibrosis in inflammatory diseases: targeting the exposed extracellular matrix. 2019 Apr 13;9(10):2868-2881.

3-Borst O, Gawaz M. Glycoprotein VI – novel target in antiplatelet medication. Pharmacol Ther. 2021 Jan;217:107630.

14 comments

Posts Carousel

Deje un comentario

Registrese para comentar. Sus e-mail no será publicados

Cancel reply

14 Comments

  • Jred Hatty
    agosto 3, 2022, 6:46 pm

    I TESTED POSITIVE FOR HSV-2 A FEW MONTHS AGO.
    At first, Yes, I was devastated thinking I have an incurable STD for life. After doing hours of research I quickly realized genital herpes is a filthy parasite that just likes to hide in your body. Yes, There’s no “medical cure” but that doesn’t mean your body can’t get rid of it. I literally flush it out of my system with the help of Doctor Azuka, A natural herbal medicine which I ordered after doing some research. And now I’m HSV-2 negative, I never believed it until my doctor finally gave me the test results and behold I was HSV-2 free. I’m so glad that I found you, Doctor Azuka. Thanks so much for your goodness I’m grateful. You can also get your help from him through his
    Email } dr.azukasolutionhome@gmail.com
    WhatsApp } +2349166175418

    REPLY
  • Mavis Wanczyk
    julio 24, 2023, 8:36 am

    Being the winner of a multi-million dollar lottery certainly will be a life-changing event for almost every single lottery winner. My name is Mavis Wanczyk from Chicopee, Massachusetts, the famous PowerBall lottery winner of $758 million (£591m). I know many people would wonder how I had won the lottery. Would you believe me if I told you that I did it with spell casting? I met this famous spell caster known as Doctor Odunga and he was the one who did it for me. As shocking as it was to me, my famous comment to the press was “ I’m going to go and hide in my bed.” Never did I believe that Doctor Odunga made me wealthy overnight. If you want to have your chance of winning and becoming very wealthy just like me, contact Doctor Odunga at odungaspelltemple@gmail.com OR WHATS-APP HIM at +2348167159012 and you will be lucky. Thanks for reading and hope to see you at the top

    FIX THE FOLLOWING PROBLEMS TO ALL ACROSS THE
    GLOBE ON:

    Get your ex back spell
    Lottery Spell
    Love/Reunion Spell
    Pregnancy Spell
    Protection Spell
    Freedom From Prison Spell
    Marriage spell
    Killing/Revenge spell
    Healing/Cure spell

    Contact him for any of these today at:
    EMAIL: odungaspelltemple@gmail.com OR Call and WHATS-APP HIM +2348167159012

    REPLY
  • Nombre y Apellidjuwano *
    julio 24, 2023, 11:33 am

    TESTIMONY ON HOW I GOT CURED TOTALLY FROM HERPES VIRUS BY DR ISHIAKU HERBS

    I want to inform the public how I was cured of herpes  Virus by a Doctor called Dr ISHIAKU. I visited different hospitals but they gave me a list of drugs like Famvir, Zovirax, and Valtrex which are very expensive to treat the symptoms and never cured me. I was browsing through the Internet searching for remedies on Herpes and I saw comments of people talking about how Doctor Ishiaku cured them. I Was scared because I never believed in the Internet but I was convinced to give him a try because I had no hope of being cured of herpes so I decided to contact him on his email, i searched his email on the net and I saw a lot of people testifying about his goodness. When I contacted him he gave me hope and sent a Herbal medicine to me that I took and it seriously worked for me, am a free person now without any problems, my HERPES result came out negative. You can contact him on his email: (ishiakuherbalcure@yahoo.com)or what – sapp him via +2348180828544 and get all your problems solved.
    1)Sickness of any kind
    2)Help to cure  HEPATITIS B, DIABETICS, HIV/AIDS  and BIPOLAR
    3)Divorce, Breakup problem, To Re-unit or to cast a spell
    4)Pregnancy problem
    5)Financial problem and Job promotion
    6)bad mouth odour or tooth problem
    7)eye or ear problem etc.

    REPLY
  • Nombre y Apellidjuwano *
    julio 24, 2023, 11:33 am

    TESTIMONY ON HOW I GOT CURED TOTALLY FROM HERPES VIRUS BY DR ISHIAKU HERBS

    I want to inform the public how I was cured of herpes  Virus by a Doctor called Dr ISHIAKU. I visited different hospitals but they gave me a list of drugs like Famvir, Zovirax, and Valtrex which are very expensive to treat the symptoms and never cured me. I was browsing through the Internet searching for remedies on Herpes and I saw comments of people talking about how Doctor Ishiaku cured them. I Was scared because I never believed in the Internet but I was convinced to give him a try because I had no hope of being cured of herpes so I decided to contact him on his email, i searched his email on the net and I saw a lot of people testifying about his goodness. When I contacted him he gave me hope and sent a Herbal medicine to me that I took and it seriously worked for me, am a free person now without any problems, my HERPES result came out negative. You can contact him on his email: (ishiakuherbalcure@yahoo.com)or what – sapp him via +2348180828544 and get all your problems solved.
    1)Sickness of any kind
    2)Help to cure  HEPATITIS B, DIABETICS, HIV/AIDS  and BIPOLAR
    3)Divorce, Breakup problem, To Re-unit or to cast a spell
    4)Pregnancy problem
    5)Financial problem and Job promotion
    6)bad mouth odour or tooth problem
    7)eye or ear problem etc.

    REPLY
  • Adrean Abelard
    septiembre 16, 2024, 6:03 am

    Have you lost hope of ever recovering your money from scam brokers? I have good news for you and yes it is 97% possible for you to recover your money through a Certified Recovery Expert CYBER ASSETS WIZARD RECOVERY, I had lost over $128,000 to a fake broker and I lost hope of ever making profit through binary trading. After the loss, I had a long research on how to recover the lost funds, I came across CYBER ASSETS WIZARD RECOVERY,   a Specialized Crypto Recovery Expert who helped Scam Victims recover their Lost Funds. After submitting my case the expert worked on my case and all my funds were recovered back. to anyone looking for Recovery firm to Recover your lost Crypto. You can contact  CYBER ASSETS WIZARD RECOVERY, VIA EMAIL ON cyberassetswizardrecovery@gmail.com

    REPLY